Preparation of 7,11-diketo-steroids



United States Patent PREPARATION OF 7,11-DIKETO-STEROIDS John M. Chemerda, Metuchen, N.J., assiguor to Merck & Co., 1nd, Rahway, NJ., a corporation of New Jersey No Drawing. Original application August 3, 1951, Se-

rial No. 240,281, now Patent No. 2,749,337, dated June 5, 1956. Divided and this application October 5, 1953, Serial No. 384,317

9 Claims. (Cl. 260-23955) This invention is concerned generally with steroid compounds having an oxygen atom attached to the carbon atom in the ll-position of the molecule. More particularly, it relates to 7-keto-l1-(keto, hydroxy or acyloxy) cyclopentanopolyhydrophenanthrene compounds, and with processes for preparing these compounds starting with the corresponding A -7-keto-ll-(hydroxy, bromo or acyloxy)-cyclopentanopolyhydrophenanthrene compound. The 7-keto-11-(keto, hydroxy or acyloxy)- cyclopentanopolyhydrophenanthrene compounds thus obtained are valuable as intermediates in the synthesis of steroid hormones having an oxygen atom attached to the ll-carbon atom, such as the adrenal hormones corticosterone, cortisone and Compound F.

This application is a division of my co-pending application, Serial No. 240,281, filed August 3, 1951, now Patent No. 2,749,337, issued June 5, 1956.

The 7-keto-11-(keto, hydroxy or acyloxy) -cyclopentan0- polyhydrophenanthrene compounds subject of the present invention have at rings B and C the following chemical structure:

R t \l -0 wherein R represents a keto, hydroxy or acyloxy substituent.

These 7-keto-11-(keto, hydroxy or acyloxy) -cycl0- pentanopolyhydrophenanthrene compounds can be prepared as follows: A A -7-keto-1l-acyloxy-cyclopentanopolyhydrophenanthrene compound (Compound 1 hereinbelow) or a A -7-keto-11-hydoxy-cyclopentanopolyhydrophenanthrene compound (Compound 2) is reacted with a reducing agent thereby forming, respectively, the corresponding 7-keto-11-acyloxy-cyclopentanopolyhydrophenanthrene compound (Compound 3) or the corresponding 7-keto-l1-hydroXy-cyclopentanopolyhydrophenanthrene compound (Compound 4); alternatively, if desired, the 7-keto11-hydroxy-cyclopentanopolyhydrophenanthrene compound can be prepared by reacting the 7- keto 11 acyloxy cyclopentanopolyhydrophenanthrene compound with a' hydrolyzing agent; this 7-keto-11-hydroxy cyclopentanopolyhydrophenanthrene compound (Compound 4) is then reacted with an oxidizing agent to produce the corresponding 7,11-diketo-cyclopentanopoly hydrophenanthrene compound (Compound 5); alternatively, said 7,1l-diketo-cyclopentanopolyhydrophenanthrene compound can be prepared by reacting the corresponding A -7-keto-11-hydroxy-cyclopentanopolyhydrophenanthrene compound (Compound 2) with an alcoholic alkali metal hydroxide at an elevated temperature of approximately 150 C.; or if desired by reacting the correspending A -7-keto-1 1-bromo-cyclopentanopolyhydrophenanthrene compound (Compound 6) with an alcoholic solution of a mineral acid.

The reactions indicated hereinabove may be chemically represented, insofar as rings B and C are concerned, as

follows:

R O l R O l Reducing V 0 agent Compound 1 Compound 3 l Hydrolyzlng agent H0 H0 Reducing 0 agent 0 Compound 2 Compound 4 A1 h 11 Alkal' 150 C. il et l Hydroiride lggg Br 0 Alcoholic Mineral Acid O 0 Compound 6 Compound 5 wherein R is an acyl radical.

The A -7-keto-11-(hydroxy or acyloxy)-cyclopentanopolyhydrophenanthrene compounds which we ordinarily employ as starting materials in connection with the presently invented process are those having a sterol side chain attached to the carbon atom in the 17-position of the molecule such as A -7-keto-1l-hydroxy-ergostadiene, A -3,1 1-dihydroxy7-keto-ergostadiene, A 6,1 1- diacycloxy-7-keto-ergostadiene, A -3,11-dialkanoxy-7- keto-ergostadiene, A -3,11 diacetoxy-7-keto-ergostadiene, A -7-keto-ll-hydroxy-cholestene, A -3,11-dil1ydroxy-7-keto-cholestene, A -3, 1 1-diacyloXy-7-keto-cholestene, A '-3,11-dialkanoxy-7-keto-cholestene, A 3, 1 1-diacetoxy-7-keto-cholestene, A (9)1228 ,1 l-dihydroxy- 7-keto-stigmastadiene, A -3,1l-diacyloxy-7-ketoestigmastadiene, A -3,l1-dialkanoXy 7 keto-stigmastadiene, A -3,11-diacetoxy 7-keto-stigmastadiene,Va bile acid side chain attached to the 17-carbon atom such as A 3,l1-di.hydroxy-7-keto-cholenic acid, A -3,11-di: acyloxy-7-keto-cholenic acid, A -3,l1-dihydroxy-7-ketoallocholenic acid, A -3,11-diacyloXy-7-keto-allocholenic acid, a degraded bile acid side chain attached to the 17 carbon atom such as A 3,11 dihydroxy 7- keto bisnorcholenic acid, A 3,11 diacyloxy 7- keto-bisnorcholenic acid, A -3,11-dihydroxy-7-keto-bisnorallocholenic acid, A -3,11-diacyloxy-7-keto-bisnorallocholenic acid, a 17-carboxyl substituent such as A 7-keto-1l-hydroxy-etiocholenic acid, A -3,l1-dihydroXy 7-keto-etiocholenic acid, A -3,11diacyloxy-7-keto-etiocholenic acid, A -3,11 dihydroxy-7-keto-etioallocholenic acid, A -3,11-diacyloxy-7-keto-etioallocholenic acid, a

' 17-acetyl substituent such as A -3,11-dihydroXy-7-ketoacyloxy-dehydrotigogenin acylate, A -7-keto.-l1-alkanoxy-dehydrotigogenin alkanoate, A -7-keto-11-acetoxydehydrotigogenin-acetate and the like. These starting materials can be prepared according to the procedures set forth in detail in my co-pending application Serial No. 240,052, filedrAugust 2, 1951, now Patent No. 2,734,897, issued February 14, 195 6, The A -7-keto-11-(acyloxy or hydroxy)-cyclopentanopolyhydrophenanthrene starting material is reacted with a reducing agent to produce the corresponding 7-keto-11-(acyloxy or hydroxy)-cyclopentanopolyhydrophenanthrene compound. This reduction reaction is ordinarily carried out by bringing the A -7-keto-11-(acyloxy or hydroxy) -cyclopentanopolyhydrophenanthrene compound into intimate contact with zinc dustand acetic acid or, if desired, hydrogen in the presence of a platinum catalyst. The 7-keto-11-(acyloxy or hydroxy) cyclopentanopolyhdrophenanthrene compounds obtained according to this reduction procedure include A e 7 keto-1l-acyloxy-ergostene, A -3,11-dihydroxy 7 keto-ergostene, A -3,11-diacyloxy-7-keto-ergostene, A -3,11-dialkanoxy-7-keto-ergostene, A -3,1l-diacetoxy 7-keto-ergostene, 7-keto-1l-acyloxy-cholestane, 7- 'keto-l l-hydroxy-cholestane, 3,11 dihydroxy-7keto-cholestane, 3,11-diacyloxy-7-keto-cholestane, 3,11-diall1anoxy- 7-keto-cholestane, 3,11-diacetoxy-7-keto-cholestane, A 3, 1 1-dihydroxy-7-keto-stigmastene, A 31 1-diacyloxy-7- keto-stigmastene, A 31l-diacetoxy-stigmastene, 3,11-dihydroxy-7-keto-cholanic acid, 3,1l-diacyloxyJ-keto-cholanic acid, 3,11-dia1kanoxy-7-keto cholanic acid, 3,11-diacetoxy-7-keto-cholanic acid, 3,1'1-dihydroxy-7-keto-allocholanic acid, 3,11-diacyloxy-7-keto-allocholanic acids, 3,11-dihydroxy;7-keto-bisnorcholanic acid, 3,1 L-diacyloxy- 7-keto-bisnorcholanic acid, 3,11-dialkanoxy 7-keto-bisnorcholanic acid, 3,11-diacetoxy-7-keto-bisnorcholanic acid, 3,11-dihydroxy-7-keto-bisnorallocholanic acid, 3,11-diacyloxy-7-keto-bisnorallocholanic acid, 3,11-dihydroxy-7-ketoetiocholanic acid, 3,11-diacyloxy-7-keto-etiocholanic acid, 3,11-diacetoxy-7-keto-etiocholanic acid, 3,11-dihydroxy-7- keto-etioallocholanic acid, 3,11-diacyloxy-7-keto-etioallocholanic acid, 3,11-dihydroxy-7-l eto-pregnane, 3,1'1-diacyloxy-7-keto-pregnane, 3,11-diacetoxy-7-keto-pregnane,

-3, 11 dihydroxy -7- keto-allopregnane, 3,11rdiacylox'y-7- keto-allopregnane, 3,11-diacyloxy-7-keto-allopregnane, 7'! keto-1I-hydroxy-tigogenin, 7-keto-11-acyloxy tigogenin acylate, 7-keto-11-alkanoxy-tigogenin alkanoate, 7-ketoll-acetoxy-tigogenin acetate, and the like. Where the A -7-ketocyclopentanopolyhydrophenan: threne compound utilized as starting material in the reduction procedure described hereinabove contains an acyloxy substituent in the ll-position thereby producing the corresponding 'A -7-keto-1l-acyloxy-cyclopentanopolyhydrophenanthrene, this latter compound can be converted to the corresponding 7-keto-11-hydroxy-cyclopentanopolyhydrophenanthrene compound, if desired, by reaction with a hydrolyzing agent. We ordinarily utilize as the hydrolyzing agent in carrying out this reaction, an alcoholic solution ofan alkali metal hydroxide such as ethanolic potassium hydroxide, methanolic potassium hydroxide, methanolic sodium hydroxide, and the like.

The 7 keto 11 hydroxy cyclopentanopolyhyidros phenanthrene compound is then reacted with an oxidizing agent, such as chromic acid, thereby forming the corresponding 7,11 diketo cyclopentanopolyhydrdphenanthrene compound. This oxidation reaction, Where chromic acid is used as the oxidation agent is conveniently conducted by dissolving 7 keto 11 hydroxy cyclopentanopolyhydrophenanthrene compound in an organic solvent substantially inert to chromic acid such as acetone, adding to the resulting solution a solution containing chromic acid dissolved in aqueous sulfuric acid, and allowing the'mixture to react substantially at room temperature for a period of approximately one hour. In accordance with this procedure, there is obtained the desired 7,1 1-diketo-cyclopentanopolyhydrophenanthrene compound such as A 7,11 diketo .ergostene, A a 3- acyloxy 7,11 diketo ergostene, A 3 acetoxy 7,11- diketo ergostene, A 3 hydroxy 7,11 diketoengostene, 7,11 diketo cholestane, 3 acyloxy 7,11- diketo cholestane, 3 acetoxy 7,11 diketo cholestane, 3 hydroxy 7,11 diketo cholestane, A 3 hydroxy- 7,11 diketo stigmastene, A 3 acyloxy 7,11 diketostigmastene, A 3 acetoxy 7,11 diketo stigmastene, 3 hydroxy 7,11 diketo cholanic acid, 3 acyloxy- 7,11 diketo cholanic acid, 3 acetoxy 7,11 diketocholanic acid, 3 hydroxy 7,11 diketo allocholanic ,acid, 3 acyloxy 7,11 diketo allocholanic acid, 3-

acetoxy 7,11 diketo allocholanic acid, 3 hydroxy- 7,11 diketo bisnorcholanic acid, 3 acyloxy 7,11- diketo bisnorcholanic acid, 3 hydroxy 7,11 diketobisnorallocholanic acid, 3 acyloxy 7,11 diketo bisnorallocholanic acid, 3 hydroxy 7,11 diketo etiocholanic acid, 3 acyloxy 7,11 diketo etiocholanic acid, 3 acetoxy 7,11 diketo etiocholanic acid, 31 hydroxy 7,11 1 diketo etioallocholanic acid, 3 acyloxy: 7,11 diketo etioallocholanic acid, 3 hydroxy 7,11- diketo pregnane, 3 acyloxy 7,11 diketo pregnane, 3 hydroxy 7,11 diketo allopregnane, 3 acyloxy? 7,11 diketo allopregnane, 7,11 diketo tigogenin, 7,11 diketo tigogenin acylate, 7,11 diketo tigogenin alkanoate, 7,11 diketo tigogenin acetate, and the like.

Alternatively, these 7,11 diketo cyclopentanopolyhydrophenanthrene compounds can be prepared by heating the corresponding A 7 keto 11 hydroxy cy clopentanopolyhydrophenanthrene compound with an alcoholic solution ofan alkali metal hydroxide at an elevated temperature. involves the rearrangement of the hydrogen atoms attached respectively to the C-11-carbon atom and to the oxygen of the ll-hydroxy substituent to. the carbon atoms in the 8 and 9-positions thereby saturating the A -double bond. 'It is ordinarily preferred to conduct this reaction by heating the A 7 keto 11 a hydroxy cyclopentanopolyhydrophenanthrene compound 'with the alcoholic solution of an alkali metal hydroxide such as ethanolic potassium hydroxide, methanolic potassium hydroxide, methanolic sodium hydroxide, and the like, at a temperature of approximately C, At this temperature the reaction is ordinarily substantially complete after a heating period of approximately eight hours.

Instead of utilizing A 7 keto 11 (acyloxy or hydroxy) cyclopentanopolyhydrophenanthrene compounds as starting materials for the preparation of the desired 7,1 l-diketo-cyclopentanopolyhydrophenanthrene;

compounds, We employ, instead, the corresponding A 7 keto 11 bromo cyclopentanopolyhydrophenanthrene compound, such as A 7 keto 11 bromoergostadiene, A 3 hydroxy 7 keto 11 bromoergostadiene, A 3 acyloxy 7 keto 11 bromo ergostadiene, A a 3 alkanoxy 7 keto 11 bromoergostadiene, A 3 acetoxy- 7 keto 11 bromoergostadiene, A -7 keto l1 bromo cholestene, A 3 hydroxy 7 keto l1 bromo cholestene,. A 3 acyloxy 7 keto 11 bromo cholestene, A 3 alkanoxy 7 keto 11 bromo cholestene,

A 3 acetoxy 7 keto 11 bromo cholestene,. s 9 ,22

mastadiene, A 3 alkanoxy 7 keto 11 bromostigmastadiene, A 3 alkanoxy 7 keto 11 bromo stigmastadiene, A 3 acetoxy 7 keto 11- bromo stigmastadiene, A 3 hydroxy 7 keto llbromo cholenic acid, 13 3 acyloxy 7 keto e 11- bromo cholenic acid, A 3 hydroxy 7 keto 11- bromo allocholenic acid, A 3 acyloxy 7 keto- 11 bromo allocholenic acid, A 3 hydroxy 7- keto 11 bromo bisnorcholenic acid, 43(9) 3 acyloxy- 7 keto 11 bromo bisnorcholenic acid, 48(9) 3 hydroxy 7 keto 11 bromo bisnorallocholenic acid, A 3 acyloxy 7 keto l1 bromo bisnorallocholenic acid, 481(5) 3 hydroxy; 7- keto 11 bromo- It will be noted that this reaction 3 hydroxy 7 keto l1 bromo stigmastadiene, A 3 acyloxy 7 keto 11 bromo stig etiocholenic acid, A 3 acyloxy 7 keto 11 bromoetiocholenic acid, A 3 hydroxy 7 keto 11 bromo etioallocholenic acid, A 3 acyloxy 7 keto- 11 bromo etioallocholenic acid, A 3 hydroxy 7- keto 11 bromo pregnene, A 3 acyloxy 7 keto- 11 bromo pregnene, A 3 hydroxy 7 keto 11- bromo allopregnene, A 3 acyloxy 7 keto 11- bromo allopregnene, A 7 keto 11 bromo dehydrotigogenin, A 7 keto 11 bromo dehydrotigogenin acylate, A 7 keto 11 bromo dehydrotigogenin alkanoate, A 7 keto 11 bromo dehydrotigogenin acetate, and the like. These compounds can be obtained by reacting N-bromosuccinimide with the corresponding A' 7 acyloxy cyclopentanopolyhydrophenanthrene compound, which in turn, can be prepared in accordance with the procedures set forth in my co-- pending application Serial No. 240,052, filed August 2, 1951. The A 7 keto 11 bromo cyclopentanopolyhydrophenanthrene compound is reacted with an alcoholic solution of a mineral acid, preferably a solution of hydrochloric acid in methanol. The reaction is conveniently carried out by heating the reactants together under reflux thereby producing the corresponding 7,11- diketo-cyclopentanopolyhydrophenanthrene compound.

The following examples illustrate methods of carrying out the present invention, but it is to be understood that these examples are given for purposes of illustration and not of limitation.

Example 1 One hundred milligrams of A -3-diacetoxy-7-ketoergostadiene (which can be prepared according to the procedure described in my co-pending application Serial No. 240,052, filed August 2, 1951), was dissolved in 5 cc. of acetic acid, 100 mg. of zinc dust was added to the solution, and the resulting mixture was heated at a temperature of 100 C. for about three hours. The reaction mixture was filtered, the filtered solution was d il ted with water, and the gummy material which precipitated was extracted with benzene. The benzene was evaporated from the benzene extract to give A -3,11-diacetoxy- 7-keto-ergostene which was obtained in the form of an amorphous solid.

The A -3,11-diacetoxy-7-keto-ergostene, prepared as described hereinabove, was dissolved in 5 cc. of a 5% solution of sodium hydroxide in methanol and the resulting solution was heated under reflux for a period of approximately one hour. The reaction solution was diluted with water and the gummy material which precipitated was recovered by decantation, washed and dried to give A -3 ,11-dihydroxy-7-keto-ergostene in the form of an amorphous solid.

The A -3,11-dihydroxy-7-keto-ergostene, prepared as described hereinabove, was dissolved in 5 cc. of acetone, and a solution containing 7 mg. of chromic acid dissolved in 1 cc. of 2 N aqueous sulfuric acid solution was added to the acetone solution. The resulting mixture was allowed to stand at room'temperature for a period of about twenty minutes, the solvents were evaporated from the reaction solution in vacuo, and the residual material was extracted with ether. The ethereal extract was chromatographed over acid-washed alumina to give substantially pure A -3-hydroxy-7,1l-diketo-ergostene; M.P. 199-200 C.

Example 2 One hundred milligrams of A -3,11-dihydroxy-7- keto-ergostadiene were dissolved in 15 cc. of alcohol, mg. of platinum oxide catalyst were added to the solution, and the resulting mixture was subjected to the action of hydrogen at a pressure of one atmosphere until one molecular equivalent of hydrogen had been absorbed. The reaction mixture was filtered, thereby removing the catalyst, and the filtered solution was evaporated in vacuo to give A -3,11-dihydroxy-7-keto-ergostene which was obtained as an amorphous solid.

The A -3,11-dihydroxy-7-keto-ergostene, prepared as described in the preceding paragraph, was dissolved in 10 cc. of acetone, and a solution containing 7 mg. of chromic acid dissolved in 1 cc. of a 2 N aqueous solution of sulfuric acid was added to the acetone solution.

The resulting mixture was allowed to stand at room Example 3 One hundred milligrams of A -3,7-diacetoxy-9,11- epoxy-ergostadiene (which can be prepared according to the procedure described in my co-pending application Serial No; 240,052, filed August 2, 1951), were heated under reflux with 5 cc. of a 5% solution of potassium hydroxide in methanol. (The alkaline methanolic reaction solution, thus prepared, contains A -3,11-dihydroxy-7-keto-ergostadiene which can be recovered therefrom, if desired, triturating the desidual solution with water, and filtering and drying the precipitated material.)

Instead of isolating the A -3,11-dihydroxy-7-ketoergostadiene, the alkaline methanolic reaction solution containing this compound was heated under pressure at a temperature of about 150 C. for a period of approximately eight hours. The reaction mixture was cooled to room temperature, water was added thereto, and the material which precipitated was recovered by filtration and purified by chromatography over acid-washed alumina to give substantially pure A -3-hydroxy-7,1l-diketoergostene; M.P. 198-200 C.

Example 4 Two hundred milligrams of A' -3,7-diacetoxyergostatriene (which can be prepared in accordance with the procedure described in my co-pending application Serial No. 240,052, filed August 2, 1951), were dissolved in 30 cc. of acetone and 280 mg. of N-bromosuccinimide and 5 cc. of water were added to the acetone solution. In a few minutes, the N-bromosuccinimide dissolved completely and a crystalline product began to separate from the solution. This material was recovered by filtration and dried to give substantially pure A 3-acetoxy-7-keto-1l-bromo-ergostadiene; M.P. ISO-153 C., dec. (using a bath preheated to C.) max. 2650 A.

Analysis.-Calcd for C H O BnBr, 14.9. Found: Br, 14.1.

Two hundred milligrams of A -3-acetoxy-7-keto-11- bromo-ergostadiene were dissolved in 30 cc. of methanol, 0.1 m1. of a 2.5 N aqueous solution of hydrochloric acid was added to the methanol solution, and the resulting solution was heated under reflux for a period of about three hours. The solvents were evaporated from the reaction solution in vacuo, and the residual material was chromato graphed over acid-washed alumina to give substantially pure A -3-l1ydroxy-7,1l-diketoergostene; M.P. 196- 198 C.

Various changes and modifications may be made in carrying out the present invention without departing from the spin't and scope thereof. Insofar as these changes and modifications are within the purview of the annexed claims, they are to be considered as part of my invention.

I claim:

1. The process which comprises reacting a 7-keto-11- acyloxy-cyclopentanopolyhydrophenanthrene compound selected from the group which consists of A -3,11-bis(lower alkanoyloxy)-7-keto-ergostene and 7-keto-11-(lower alkanoyloxy)-tigogenin 3-(lower alkanoate) with a hydizing agent comprising chromic acid {to form the corresponding 7,11 diketo cyclopentanopolyhydrophenanthrone compound. V

'2. The process which comprises reacting A -3,;111 diacetoxy-7-keto-1ergostene with methanolic sodium hydroxide to produce 43 3-111-dihydroxy-7-keto-ergostene, and reacting said A? -3,11-dihydroxy-7 keto-ergostene with chromic acid to form A -3-hydroxy-7,11-diketoergostene.

3. The process which comprises reacting 7 keto-11- acetoXy-tigogenin acetate with .a hydrolyz'ing Jagent comprising an alcoholic solution of an alkali metal hydroxide to :produce 7-keto-1 1-hydroXy-tigogenin,. and reacting said 7-vketo-1l-hydroxy-tigogenin with an oxidizing zagentcomprising chromic acid to form 7,11=diketo-;tigogenin.

4. The process which comprises reacting a 7eketo-l1- acyloxy-cyclopentanopolyhydrophenanthrene compound selected from the group with consists of A -l3,11-his(lower alkanoyloxy)-7-keto-ergostene and 7-.keto-.1:1-(-lower alkanoyloxy)-tigogenin 3-(lower alkanoate) with ahydrolyzing agent comprising an alcoholic solution .01: an alkali metal hydroxide to produce the corresponding :7-ke'to-1'1- hydroxy-cyclopentanopolyhydrophenanthrene compound.

5. The process which comprises reacting A -3,11-diacetoxy-T-ketoergostene with a methanolic solution of sodium hydroxide to g-PEQCIUCB A -BJ1-dihydroxy-7 ketoergostene. V r V V V 6. The process which comprises reacting 7-keto1'1- acetoxytigogenin acetate with :a hydrolyzing agent comprisingan alcoholic solution of-an alkali metal hydroxide to produce -7-iketo-1;1 hydroxy-tigogenin.

7. The process whichtcomprises reacting 7-keto-11- hydroxy-rcyclopcntanopolyhydrophenanthrene compound selected from the group which consists of A -3,11-dihydroxy-7-keto-ergostene and 7-keto-11-hydroxy-tigogenin with an oxidizing agent comprising chromic acid to form ,the corresponding 7,1-1-diketo-cyclopentanopolyhydrophenanthrenecompound. V

, -8. The process which comprises reacting A -3 ,11-dihydroxy-7-keto-ergostene with chromic acid to form A- y o ys,- ;1- il to rostene.

-9.. The process which comprises reacting v7eketo-11- hydroxyatigogenin with chromic acid to form 7,11-diketo-tigogenin.

OTHER REFERENCES E1sevier"s Encyclopedia of Organic Chemistry (1952), vol. 140, suppl., pages 1275s, 1270. 

1. THE PROCESS WHICH COMPRISES REACTING A 7-KETO-11ACYLOXY-CYCLOPENTANOPOLYHYDOPHENANTHRENE COMPOUND SELECTED FROM THE GROUP WHICH CONSISTS OF $22-3,11-BIS(LOWER ALKANOYLOXY) -7-KETO-ERGOSTENE AND 7-KETO-11-(LOWER ALKANOYLOXY)-TIGOGENIN 3-(LOWE ALKANOATE) WITH A HYDROLYZING AGENT COMPRISING AN ALCOHOLIC SOLUTION OF AN AKALI METAL HYDROXIDE TO PRODUCE THE CORRESPONDING 7KETO - 11 - HYDROXY-CYCLOPENTANOPOLYHYDROPHENANATHRENE COMPOUND, AND REACTING SAID 7-KETO-11-HYDROXY-CYCLOPENTANOPOLYHYDROPHENANTHRENE COMPUNDS WITH AN OXIDIZING AGENT COMPRISING CHROMIC ACID TO FORM THE CORRESPONDING 7,11-DIKETO-CYCLOPENTANOPOLYHYDROPHENANTHRENE COMPOUND. 